Since the AIDS epidemic of the early 1980s the interest in alternatives to allogeneic blood transfusion has grown, particularly for elective surgery. One alternative that currently accounts for over 5% of the blood donated in the United States and some countries in Europe is autologous transfusion, obtained primarily by preoperative donation. In addition to preoperative blood donation, intraoperative blood salvage (IBS) (Table 1) from the surgical field represents an important option for covering transfusion demands. Along this IBS process, blood lost by a surgical patient is collected, cleaned, and made available for reinfusion to that patient.
Briefly, blood shed into the surgical field is aspirated from this site into an especially designed containment. Citrate or heparin anticoagulant is added, and the contents are centrifuged and/or filtered to remove leukocytes and clots and debris. IBS devices used can vary from simple, inexpensive, sterile bottles filled with anticoagulant to expensive, sophisticated, high speed cell washing devices (e.g. Medtronic Sequestra 1000, Cobe BRAT 2, Medtronic Autolog, Haemonetics Cell Saver-5® and Fresenius CATS®; Bentzien et al., Anaesthesist 49: 505, 2000; Serrick et al., J. Extra Corpor. Technol. 35(1): 28, 2003; Carless et al., The Cochrane Review, In: The Cochrane Library, John Wiley & Sons, Ltd., issue 3 pp. 1-180, 2010). Used in close to a million surgeries each year in the USA, the IBS procedure has become an integral part of blood management and conservation programs of hospitals (www.bloodbook.com).
TABLE 1Benchmarks of intraoperative blood salvage in cancer surgeryEfficient blood savingRelief of blood resourcesCompatibilitySupply of bloodRapid availabilityOptimal therapy for blood lossCost-efficiencyBlood loss-dependent applicationNo excess of bloodAfter at least 1 L blood losstransfusionLess deficiency inEnhanced efficacy of chemo-/radiotherapyblood transfusionHigh blood qualityWashed and fresh erythrocytesIncreased securityReduced transfusion risks (e.g. infection,transfusion error, difficult cross-match)No need for autologousDecrease costs of wasted unitspre-donationMore practicable for clinicians
Besides increased incidences of preoperative anemia, blood donation prior surgery raises serious additional economical questions due to the high overall transfusion rates (Carless et al., Transfus. Med. 14: 123, 2004). In addition, about 30% of preoperative autologous blood donations have to be discarded in Italy because not-required autologous blood products are excluded from allogeneic blood transfusions per se according to regulatory guidelines. In this regard IBS and subsequent autotransfusion generally represent safe and more cost-effective measures in blood management.
Advantages of Intraoperative Blood Salvage
In contrast to allogeneic red blood cell transfusions, IBS is considered a safe and efficacious alternative. Importantly, despite excellent viral diagnostics the risk of transferring HIV infection is 1 per 493.000 allogeneic blood transfusions, the risk of transferring hepatitis C virus infection is 1 per 103.000 and the risk of transmitting hepatitis B virus infection is 1 per 63.000 (Schreiber et al., N. Engl. J. Med. 334: 1685, 1996). Results of a ‘Serious Hazards of Transfusions’ study performed from 1996 until 2001 documented these risks of allogeneic transfusion incidences (Dzik et al., Transfusion 43: 1190, 2003). Strikingly, the transmission of infectious diseases by means of contaminated blood transfusions appears to be a minor risk compared to the enormous risks of ABO-incompatible blood due to administrative or human failure along the blood donation and transfusion process (Sazama, Transfusion 30: 583, 1990; Dzik et al., Transfusion 43: 1190, 2003). More than 70% of transfusion incidences could be attributed to incorrect transfused blood components mainly caused by administration failure and errors in sampling, prescription as well as in component collection (Dzik et al., Transfusion 43: 1190, 2003). Pre- and intraoperative autotransfusion of red blood cells bypasses per se these inherent risks of allogeneic blood transfusion. In general, autologous blood salvage techniques offer advantages but do not require infusions of crystalloid or colloid to preserve blood volume (Table 1). Many liters of blood can be salvaged intraoperatively during extensive bleeding, far more than with other autologous techniques.
Suitability of Patients for IBS
Intraoperative blood salvage has been available for over 25 years. It is used extensively in cardiothoriac surgery, vascular and trauma surgery, as well as liver transplantation. Contraindications to its use are bacterial infections and tumor cells probably shed into the blood of the surgery field, and use of microfibrillar collagen or other foreign material at the operative site. Nowadays, due to shortages of donor blood and fears of transmitted infections the use of IBS also gains great interest in cancer surgery with high blood loss. The reluctance of surgeons to use autotransfusion in cancer surgery has diminished, as reports found no increase in local recurrence or metastatic disease when compared with standard survival data (Klimberg et al., Arch. Surg. 212: 1326, 1986; Perseghin et al., Vox Sang. 72: 221, 1997). As reviewed by Vanderlinde et al. (BMJ 324: 772, 2002) red blood cell autotransfusions collected from preoperative blood donations could significantly lead to reduced infection and recurrence incidences during colorectal cancer surgery as compared to allogeneic transfusions (Table 2). Some of these reviewed clinical trials are even more important as colorectal surgeries have been per se excluded from IBS recommendations due to the inherent risk of transmitting bacterial infections.
TABLE 2Clinical outcome of randomized trials of autologous versus allogeneic transfusion*% of cases developingP value forcomplications afterreduction inNo ofType ofType oftransfusionpostoperativeStudypatientssurgeryInterventioncomplicationAutologousAllogeneiccomplicationsBusch et al, 19939423ColorectalPredepositInfection2725NSautologousdonationN. Engl. J. Med. 328: 1372, 1993Recurrence3734NSHeiss et al, 1993120ColorectalPredepositInfection1227<0.05and 199410, 14autologousdonationLancet 342: 1328, 1993Recurrence17290.11J. Clin. Oncol. 12: 1859, 1994Newman et al, 19971170KneePostoperativeInfection 634<0.05replacementautologousJ. Bone Joint Surg. Br. 79: 630, 1997salvageFarrer et al, 19971250VascularPostoperativeInfection13440.029J. Vasc. Nurs. 15: 111, 1997autologoussalvageThomas et al. 200113231KneePostoperativeInfectionNANA0.036replacementautologoussalvageBr. J. Anaesth 86: 669, 2001ReadmissionNANA0.008NS = not significantNA = not available (ie not reported).*Table is taken from Vanderlinde et al., BMJ 324: 772, 2002.
Nevertheless, a study clearly showed that tumor cells were detectable in the surgery field, although their impact on cancer recurrence remained unclear (Hansen et al., Arch. Surg. 130: 387, 1995). For instance the number of tumor cells in the peripheral blood and IBS of 61 patients with cancer surgery of an abdominal, orthopedic, urological, gynecological, or head and neck malignant tumor were compared. In 57 of 61 patients tumor cells were detected in the blood shed during oncological surgery. These tumor cells were identified by proliferation capacity, invasiveness, and tumorigenicity with a sensitivity of 10 tumor cells per 500 mL blood (Hansen et al., Arch. Surg. 130: 387, 1995). Interestingly, the number of tumor cells in the shed blood did not correlate with the amount of blood loss and only in 26% of these patients circulating tumor cells could be detected in the peripheral blood. Therefore, it is estimated that the number of tumor cells in the blood shed into the surgery field could range from 10 to 107. These results were also confirmed independently by Dale et al., Br. J. Surg. 75: 581, 1988 and Müller et al., Anaesthesist 45: 834, 1996.
To further address safety concerns about the risk of residual tumor cells in IBS samples, additional approaches are needed to effectively eliminate the contaminating tumor cells:                One method used in combination with automatic IBS devices like Cell Saver-5® is represented by additional filtration of samples through leukocytes depletion filters (e.g. Pall RC400, RCEZ1T), RC XL-1) (Bontadini et al., Transfusion 34. 531, 1994; Yaprak et al., Turk. J. Pediatr. 40: 89, 1998; Gwak et al., Liver Transplant. 11: 331, 2005). The safe transfusion of erythrocytes collected by IBS does not impair clinical outcome as evaluated in several trials (Edelman et al. Urology 47: 179, 1996; Perseghin et al., Vox Sang. 72: 221, 1996; Davis et al., BJU International 91: 474, 2003).        In a different IBS approach the samples are irradiated at 50 Gy due to the underlying principle of radiosensitivity of nucleated cancer cells and due to the radioresistance of non-nucleated red blood cells.        
Due to the complex logistic demand of this IBS/irradiation approach including additional staff requirement, dosimetry issues, suitable as well as certified irradiation equipment in the clinical department, this latter procedure is not in favor of broad application. In contrast, the filtration procedure for leukocyte depletion represents an elegant approach to reduce residual tumor cells during IBS although this technique still has the inherent risk of residual tumor cells still passing the filter.